Neuroanatomy PDF

NEUROANATOMY Sommario 1. TERMINOLOGY............................................................................................................................................. 7 2. THE NERVOUS SYSTEM – macroscopic organization....................................................................................... 7 2.1 Central Nervous System (CNS)................................................................................................................ 9 2.1.1 Grey and white matter.................................................................................................................. 11 2.1.2 Spinal cord – macroanatomy......................................................................................................... 12 2.1.3 Brain – surface anatomy............................................................................................................... 13 2.1.4 Inner brain................................................................................................................................... 15 2.2 Diencephalon...................................................................................................................................... 16 2.3 Basal ganglia........................................................................................................................................ 17 2.4 Brain stem........................................................................................................................................... 18 2.4.1 Medulla oblungata....................................................................................................................... 19 2.4.2 Pons............................................................................................................................................ 20 2.4.3 Midbrain...................................................................................................................................... 21 2.5 Cerebellum.......................................................................................................................................... 22 3. ORGANIZATIONAL PRINCIPLES OF THE CNS................................................................................................. 23 4. NERVOUS PATHWAYS................................................................................................................................. 24 4.1 Topographic maps............................................................................................................................... 25 5. MICROSCOPIC ANATOMY OF THE NERVOUS SYSTEM................................................................................... 26 5.1 Neurons.............................................................................................................................................. 27 5.1.1 Multipolar neurons....................................................................................................................... 29 5.1.2 Bipolar neurons............................................................................................................................ 31 5.1.3 Pseudounipolar neurons................................................................................................................ 31 5.2 The synapse......................................................................................................................................... 32 5.2.1 Neurotransmitters........................................................................................................................ 33 5.2.2 Dendritic spines............................................................................................................................ 35 5.3 Glial cells............................................................................................................................................. 36 5.3.1 Astrocytes.................................................................................................................................... 37 5.3.2 Microglia..................................................................................................................................... 40 5.3.3 Oligodendrocytes.......................................................................................................................... 42 5.3.4 Oligodendrocytes and Schwann’s cells........................................................................................... 46 5.3.5 Ependimal cells............................................................................................................................. 47 5.3.6 Satellite glial cells......................................................................................................................... 48 5.4 Gliogenesis in adult nervous tissue........................................................................................................ 48 6. PROTECTIVE LAYERS................................................................................................................................... 49 6.1 Dura mater.......................................................................................................................................... 50 6.2 Spaces................................................................................................................................................. 51 6.3 Arachnoid............................................................................................................................................ 52 6.4 Pia mater............................................................................................................................................. 53 6.5 Traumas.............................................................................................................................................. 53 6.6 Cerebral ventricles............................................................................................................................... 53 6.7 CSF or liquor........................................................................................................................................ 54 6.7.1 CSF’s circulation............................................................................................................................ 55 6.8 Hydrocephalus..................................................................................................................................... 56 7. VASCULARIZATION OF THE BRAIN............................................................................................................... 57 7.1 Arterial circulation............................................................................................................................... 57 7.1.1 Circle of Willis............................................................................................................................... 58 7.2 Venous circulation............................................................................................................................... 59 7.3 Blood Brain Barrier (BBB)...................................................................................................................... 60 7.4 Lymphatic system................................................................................................................................ 61 8. SPINAL CORD.............................................................................................................................................. 62 8.1 Macroscopic anatomy.......................................................................................................................... 62 8.1.1 Sulci and fissures.......................................................................................................................... 62 8.1.2 Neuromers................................................................................................................................... 63 8.1.3 Roots........................................................................................................................................... 64 8.2 Microscopic anatomy........................................................................................................................... 66 8.2.1 Meninges..................................................................................................................................... 66 8.2.2 Vascularization............................................................................................................................. 66 8.2.3 Grey and white matter.................................................................................................................. 67 8.2.4 Horns........................................................................................................................................... 68 8.2.5 Neuromuscolar spindle................................................................................................................. 69 8.2.6 Somatotopic organization............................................................................................................. 69 8.2.7 Neuromuscolar junction................................................................................................................ 70 8.2.8 Reflex arch................................................................................................................................... 70 9. PATHWAYS OF THE SPINAL CORD................................................................................................................ 71 9.1 Propriospinal pathways........................................................................................................................ 73 9.2 Ascending or descending pathways....................................................................................................... 73 9.3 Motor pathways.................................................................................................................................. 74 9.3.1 Pyramidal pathway....................................................................................................................... 74 9.3.2 Extrapyramidal pathway............................................................................................................... 75 9.3.3 Medial motor systems................................................................................................................... 78 9.3.4 Lateral motor systems................................................................................................................... 78 9.2 Sensory pathways................................................................................................................................ 79 9.2.1 Dorsal column system................................................................................................................... 79 9.2.2 Spinothalamic tracts..................................................................................................................... 80 9.2.3 Lateral spinothalamic tract........................................................................................................... 82 9.2.4 Spinocerebellar tracts................................................................................................................... 82 9.3 Diffusion tensor imaging (dta)............................................................................................................... 83 9.4 Motor neuron diseases........................................................................................................................ 83 9.4.1 Amyotrophic Lateral Sclerosis (ALS)................................................................................................ 83 9.4.2 Spinal Muscular Atrophy (SMA)..................................................................................................... 83 9.4.3 Spinal cord injuries........................................................................................................................ 84 10. BRAIN STEM............................................................................................................................................... 84 10.1 Development of the brainstem............................................................................................................. 85 10.2 Features of the brainstem.................................................................................................................... 86 10.3 Cranial nerves nuclei organization......................................................................................................... 88 10.4 Midbrain............................................................................................................................................. 89 10.4.1 Tegmentum.................................................................................................................................. 89 10.4.2 Substantia nigra of Soemmering.................................................................................................... 89 10.4.3 Red nucleus.................................................................................................................................. 91 10.4.4 Tectum......................................................................................................................................... 92 10.5 Pons.................................................................................................................................................... 93 10.6 Medulla oblungata............................................................................................................................... 94 10.6.1 Pyramids...................................................................................................................................... 94 10.6.2 Cranial nerves nuclei..................................................................................................................... 94 10.6.3 Reticular formation....................................................................................................................... 96 10.6.4 Locus coeruleus............................................................................................................................ 97 10.6.5 Raphe nuclei................................................................................................................................. 97 10.4 White matter....................................................................................................................................... 98 10.4.1 Sensory pathways or ascending tracts............................................................................................ 98 10.4.2 Motor pathways........................................................................................................................... 98 11. CEREBELLUM.............................................................................................................................................. 98 11.1 Morphology......................................................................................................................................... 98 11.2 Function.............................................................................................................................................. 99 11.3 Repetita iuvant.................................................................................................................................... 99 11.4 Anatomical data..................................................................................................................................100 11.5 Cerebellar peduncles...........................................................................................................................101 11.6 Lobes.................................................................................................................................................102 11.6.1 Lobules.......................................................................................................................................102 11.7 Functional regions...............................................................................................................................103 11.7.1 Anatomo-clinical summary...........................................................................................................105 11.8 Phylogenesis.......................................................................................................................................105 11.9 Microanatomy....................................................................................................................................107 11.9.1 Purkinje cells...............................................................................................................................107 11.9.2 Granule cells................................................................................................................................108 11.9.3 Interneurons................................................................................................................................108 11.10 Afferent fibres.................................................................................................................................109 11.10.1 Cerebellar glomeruli.................................................................................................................110 11.10.2 Somatotopic organization........................................................................................................111 11.10.3 Inputs......................................................................................................................................111 11.11 Efferences.......................................................................................................................................113 11.12 Cerebellar vascularization................................................................................................................113 12. DIENCEPHALON.........................................................................................................................................114 12.1 Functions...........................................................................................................................................115 12.2 Thalamus............................................................................................................................................115 12.2.1 Internal structure.........................................................................................................................116 12.3 Hypothalamus....................................................................................................................................121 12.3.1 Hypothalamic nuclei....................................................................................................................122 12.3.2 Hypothalamic control of the pituitary gland..................................................................................123 12.3.3 Vascularization of the pituitary gland............................................................................................125 12.3.4 Anterior pituitary hormones and hypothalamic factors..................................................................126 12.3.5 Modulation of the hypothalamic control of the pituitary gland.......................................................127 12.3.6 Other functions............................................................................................................................128 12.3.7 Pituitary and hypothalamic tumors...............................................................................................130 12.4 Epithalamus........................................................................................................................................131 12.4.1 Pineal gland................................................................................................................................131 12.5 Subthalamus.......................................................................................................................................132 12.5.1 Direct and indirect pathways........................................................................................................133 13. TELENCEPHALON.......................................................................................................................................133 13.1 Hemispheres......................................................................................................................................133 13.2 Frontal lobe........................................................................................................................................135 13.3 Parietal lobe.......................................................................................................................................136 13.4 Temporal lobe....................................................................................................................................137 13.5 Occipital lobe......................................................................................................................................138 13.6 Limbic lobe.........................................................................................................................................139 13.7 Cerebral cortex...................................................................................................................................140 13.8 Plasticity of the cerebral cortex........................................................................................................141 13.8.1 Cerebral lateralization..................................................................................................................141 14. TELENCEPHALIC WHITE MATTER................................................................................................................141 14.1 Corpus callosum.................................................................................................................................142 14.1.1 Clinical reference.........................................................................................................................143 14.2 Anterior commissure...........................................................................................................................143 14.3 Hippocampal commissure or psalterium..............................................................................................143 15. BASAL GANGLIA.........................................................................................................................................146 15.1 Development of the basal ganglia........................................................................................................150 15.1.1 Modular organization of the neostriatum......................................................................................150 15.2 Inputs & Outputs................................................................................................................................151 15.2.1 Afferences...................................................................................................................................151 15.2.2 Efferences...................................................................................................................................151 15.3 Circuits...............................................................................................................................................151 15.3.1 Extrinsic circuits...........................................................................................................................151 15.3.2 Intrinsic circuits...........................................................................................................................154 15.4 Pathologies of the basal ganglia...........................................................................................................154 15.4.1 Parkinson’s disease......................................................................................................................155 15.4.2 Injuries to subthalamic nucleus – Hemiballismus............................................................................155 15.4.3 Huntington’s disease....................................................................................................................155 16. LIMBIC SYSTEM..........................................................................................................................................156 16.1 Emotions............................................................................................................................................156 16.2 Organization.......................................................................................................................................157 16.3 Limbic cortex......................................................................................................................................158 16.3.1 Cingulate cortex..........................................................................................................................159 16.3.2 Hippocampal formation...............................................................................................................159 16.4 Hippocampus and memory..................................................................................................................163 16.4.1 Memory......................................................................................................................................163 16.4.2 HM patient..................................................................................................................................164 16.4.3 Hippocampus and spatial memory................................................................................................164 16.4.4 Lateralization of functions............................................................................................................165 16.4.5 Functions of the anterior and posterior hippocampus.....................................................................165 16.5 Pathologies.........................................................................................................................................165 16.5.1 Alzheimer’s disease......................................................................................................................166 16.5.2 Epilepsy.......................................................................................................................................166 16.5.3 Ischemia.....................................................................................................................................166 16.4 Other structures connected to the limbic system..................................................................................166 16.4.1 Amygdala....................................................................................................................................167 16.4.2 Basal ganglia – nucleus accumbens..............................................................................................169 17. PNS...........................................................................................................................................................170 17.1 Nervous plexuses................................................................................................................................173 17.2 Cranial nerves.....................................................................................................................................175 18. ANS...........................................................................................................................................................179 18.1 Organization.......................................................................................................................................179 18.2 Functions...........................................................................................................................................181 19. EYES – SIGHT.............................................................................................................................................182 19.1 Fibrous tunic.......................................................................................................................................183 19.1.1 Cornea........................................................................................................................................184 19.2 Vascular tunic.....................................................................................................................................185 19.2.1 Choroid.......................................................................................................................................187 19.2.2 Iris..............................................................................................................................................187 19.2.3 Ciliary body.................................................................................................................................188 19.2.4 Crystallin lens..............................................................................................................................191 19.3 Vitreous body.....................................................................................................................................192 19.4 Retina................................................................................................................................................193 19.4.4 Distribution of neurons................................................................................................................193 19.4.2 Microvilli RPE and receptors.........................................................................................................195 19.4.3 Photoceptors...............................................................................................................................196 19.4.4 Bipolar cells.................................................................................................................................203 19.4.5 Horizontal cells............................................................................................................................203 19.4.6 Amacrine cells.............................................................................................................................204 19.4.7 Intrinsically photosensitive ganglion cells and circadian rhythms....................................................204 19.4.8 Glial cells in the retina..................................................................................................................204 19.4.9 Visual defects..............................................................................................................................205 19.4.10 Fundus ophthalmoscopy...........................................................................................................206 19.4.11 Vascularization of the eye.........................................................................................................207 19.5 Visual Pathways..................................................................................................................................208 19.5.2 Retina-geniculate-striate pathway................................................................................................212 19.5.3 Retina-tectum-pulvinar-extrastriate pathway................................................................................217 20. EARS – EARING..........................................................................................................................................219 20.1 Ear.....................................................................................................................................................219 20.1.1 External ear.................................................................................................................................219 20.1.2 Middle ear...................................................................................................................................220 20.1.3 Inner ear.....................................................................................................................................224 20.2 Vestibular system...............................................................................................................................229 20.2.1 Membranous labyrinth – ampullae...............................................................................................229 21. TASTE & SMELL..........................................................................................................................................230 22. MICROSCOPY.............................................................................................................................................231 22.1 First microscopes................................................................................................................................231 22.2 Space resolution.................................................................................................................................231 22.2.1 Measurement of resolution..........................................................................................................232 22.3 EM in biology......................................................................................................................................233 22.3.1 Preparation of a sample for EM vs LM...........................................................................................234 Before getting started, here’s a mini picture of the anatomical planes (for you guys and for me, because I suck with these things and I need a reminder). 1. TERMINOLOGY Centre: neurons (somata) involved in a common function. Nucleus/nuclei: refers to a group of neurons (somata) that have a common function and are also delimited by specific anatomical boundaries. Tract: group of CNS axons that share same origin (usually a nucleus), destination and function Fascicles/column: fascicle is a smaller group, columns is a wider group of axons located in a specific part of the spinal cord’s white matter. Nerve: group of PNS axons Ganglion/ganglia: enlargement along the course of the nerves which includes the cell somata of PNS neurons. 2. THE NERVOUS SYSTEM – macroscopic organization Central nervous system (CNS). Brain and spinal cord, hosted in the dorsal cavity of the body, that includes the skull (contains the brain) and the vertebral canal within the spine (hosts the spinal cord). The CNS receives sensory information from outside (smell, hearing, sight...) and inside (proprioception), processes it and produces an output that’s meant to control other systems. Peripheral nervous system (PNS). Nerves (fascicles of axons) that connect the CNS with the other organs. Within the PNS we have cranial nerves (connecting body and brain directly) and spinal nerves (connecting spinal cord with organs). We can also include ganglia, structures associated to the nerves; the nerves included in the ganglia are those from which the axons originate (?). Autonomic nervous system (ANS). Part of CNS and PNS devolved to the control of the visceral activity (heart frequency, respiratory frequency/speed, accommodation of the lens in the eyes to focus, activity of glands for lacrimation/salivation…). It’s autonomous from our will, therefore autonomic. It includes the enteric nervous system, a net of neurons within the layers of our gut and controls its contraction. Our body collects information from the outside and itself through different receptors for: 1. Specific sensitivity: “5 senses” except for touch. There are organs which goal is just to collect such sensory information. 2. Enteroception or visceral sensitivity: regarding our internal organs, about the state of organs (including conscious and unconscious sensitivity). These kind of stimuli become conscious only when it has reached a certain threshold of intensity. 3. Somatic sensitivity: including touch (both with “high” and “low” resolution; spatial and temporal resolution), thermal sensitivity, pain (nociception) and proprioception (sense of the position of different parts of the body (at rest and moving). Proprioception is monitored by receptors inside muscles and along (tendini). The sensory info is conveyed to the CNS by the PNS (afferent elements). The info reaches the CNS and is elaborated. The CNS then produces a response to the stimulus that is carried through the body to the target tissues always by PNS, that can be: Somatic nervous system (skeletal muscles) Autonomic nervous system (heart muscles, smooth muscles and glands) o Parasympathetic: decrease heart rate and contraction strength o Sympathetic: induces an acceleration of heart rate and strengthen its muscles 2.1 Central Nervous System (CNS) Composed by brain and spinal cord. Sagittal section (medial section) The brain includes different parts (listed here from caudal to cranial): Brain stem: an axial continuation of the spinal cord. There is no real boundary between its 3 components. Anatomists conventionally set a boundary between stem and spinal cord at the first joint of the first vertebra and the skull (atlanto-occipital joint). o Medulla oblungata o Pons o Midbrain Cerebellum: caudal to the brain stem Diencephalon: just above the midbrain, composed by grey matter nuclei located deep into the brain Telencephalon: also contains the basal ganglia Development of the nervous system The development of the nervous system is very early, starts in the 3 rd week post conception. First thing is the formation of the neural plate in the medial part of the embryo. The notochord, just below, produces specifying factors that induce a different type of tissue that becomes the neural plate. Later on, it forms the neural tube. In this process, some cells migrate laterally from the tube to form 2 lateral masses of cells, called neural crests. These will give rise to the structure of the PNS, while the neural tube will become brain and spinal cord. The tube develops anteriorly in 3 vesicles: prosencephalon, mesencephalon, rombencephalon. The caudal part will become the spinal cord. These vesicles progressively change shape and give rise to other vesicles. Prosencephalon: 2 lateral vesicles called telencephalon, and a third vesicle called diencephalon Mesencephalon: stays as it was Rombencephalon: produces 2 structures called metencephalon and myelencephalon Qua ho perso roba, vedi registrazione (spoiler, non ha registrato, lol) Telencephalon: cortex and basal ganglia Diencephalon: thalamus, epithalamus, subthalamus Mesencephalon: midbrain Metencephalon: pons and cerebellum Myelencephalon: medulla oblungata Later on, the internal empty cavity of the vesicles will become the internal ventricles in the adult brain containing liquor (cerebro-spinal fluid, CSF): The 2 lateral ventricles Third ventricle maintains the name, inside the diencephalon Fourth ventricle in the caudal part between the pons and the cerebellum From the 3rd vesicle originate the retinas and optic nerves. Optic nerves bring info from the external environment; because of that they should be part of the PNS, but they technically originated from the CNS (in fact they’re myelinated by oligodendrocytes, differently from the rest of the PNS’s axons that are myelinated by Schwann cells). During the development, the telencephalon grows super huge (he’s over 9000!) and covers all the other brain structures. The cortex starts to gyrify at 6 months from conception. During the development process, the embryo bends forward and the parts of the tube “fall” forward thanks to 2 flexures (cervical flexure and cephalic flexure). This bending determines the position of the brain (and eyes) in relation of the body which characterizes the bipedal position. As a result of this folding, we shift of 90° of all the positional indications (rostral, caudal, posterior, anterior). (The black arrows aren’t technical terminology, it’s just to understand the directions. The red arrows are for “usual” anatomical descriptions. Yellow arrows are for CNS anatomical descriptions). 2.1.1 Grey and white matter The distinction between grey and white matter is based on the distribution of the cell bodies (somata) of neurons and glial cells. Somata are located in the grey matter (cortex). Most axons are included in the white matter (so called because of the colour of myelin, white-yellowish). Myelin staining (we highlight myelinated axons)/Nissl staining (we see cell somata) Sì vabbè, sta parte me la sono un pochino persa. Come la prof si è persa la registrazione :’) The cortex is about 2 – 4 mm thick. Below the cortex (grey matter) there’s a huge extension of white matter. This includes axons that connect the 2 hemispheres (corpus callosum) and axons that reach part of the brain stem and spinal cord (descending/ascending axons). In the deeper part of the telencephalon, there is other grey matter, composed by nuclei in diencephalon and basal ganglia. The cerebellum has a grey matter layer (cerebellar cortex) and an inner part of white matter that creates tiny folds resembling branches of a tree (that’s why it’s called arbor vitae?). In the deeper part of the cerebellum there are nuclei of grey matter called deep cerebellar nuclei. The exact opposite in the spinal cord. Here the white matter is on the outside part, while grey matter (cell bodies) is in the inner part. The grey matter has a butterfly shape. Its parts are differentiated, both anatomically and functionally (dorsal, ventral, ecc). 2.1.2 Spinal cord – macroanatomy It’s located in the vertebral canal but it doesn’t occupy its entire extension: it stops at L1 – L2 vertebrae. The spine grows more and for more time compared to the spinal cord. It can be divided in different portions, more or less corresponding to the different part of the spine: Cervical: 8 neuromeres (neuromeri) Thoracic: 12 neuromeres Lumbar: 5 neuromeres Sacral: 5 sacral neuromeres and 1 coccygeal segment (reached by a single pair of spinal nerves) Ho perso della roba qua The spinal cord is involved in transferring sensory info to the brain, crucial to the motor control (voluntary and autonomic reflexes). There are both ascending pathways (sensory) and descending pathways (motor). Since it finishes at L1 – L2, the rest is “empty” (not filled by spinal cord); that “space” is called lumbar cisterna, where it’s possible to collect CSF for diagnostic purposes. This portion is still occupied by spinal nerves that arise from the last lumbar neuromeres. It’s to be known that some nerves that arise from the lumbar tract have to exit the spine at a lower level to reach their target organs; therefore, they descend vertically all together in a structure called cauda equina (tipo se il nervo è al piano giusto esce e bona, se invece deve scendere va giù in verticale, producendo con tutti gli altri una “coda” di nervi detta cauda equina). A pair of spinal nerves, 1 left 1 right. Approaching the spinal cord, the nerves divide, each in 2 branches called roots (dorsal and ventral roots). Even closer to the cord, they divide again in ramicles. Roots are functionally different: dorsal includes incoming axons that bring sensory info, while ventral root includes axons that are exting from the ventral part of the spinal grey matter and bring info related to the motor control (skeletal muscles, smooth muscles, cardiac muscles, glands). Along the course of the dorsal root, we can appreciate small enlargements that are the ganglia associated to them; here are the cell somata of neurons that collect sensory info from the periphery first (first sensory neurons). In the spinal cord we can appreciate 2 enlargements: in the cervical tract (cervical enlargement) and in the lumbar tract (lumbosacral enlargement). Here the spinal cord is larger (not because of the ganglia, it’s just bigger), corresponding to the incoming/outcoming nerves for sensory info/motor control of upper and lower limbs. Experiment of Rita Levi Montalcini on chicken embryos Rita Levi Montalcini, together with Giuseppe Levi and Viktor Hamburger, conducted experiments on chicken embryo to better understand motor neurons. They amputated a wing bud in the embryos, which resulted in the absence of its related motor neuron (that, normally, innervates the wing). They also tried the opposite experiment: they transplanted an addictional wing bud and obtained an addictional motor neuron and a bigger enlargement of the spinal cord 🡪 The cells in the spinal cord receive signals from the organs that they’re meant to innervate: skeletal muscles release growth factors that help the development of nervous system, modulate its differentiation and survival. At least one of these neurotrophins is NGF (she won the Nobel prize for its discovery). In the spinal cord we can identify 2 fissures that divide it in 2 halves (right and left): a dorsal medial septum and a ventral medial septum, called antimers. There are also lateral fissures: dorsal-lateral (allows the entrance of the dorsal roots) and ventral-lateral (where roots exit from the spinal cord). We can also notice a central canal, the remaining of the inner part of the neural tube. 2.1.3 Brain – surface anatomy The brain is divided in 2 hemispheres: left and right, subdivided by the interhemispheric fissure. Cutting along the central line we can appreciate the medial surface of the brain called interhemispheric surface. Dividing the two hemispheres and opening the brain, we discover that, for the most part, it's made of cerebral cortex. Below it, there’s a white matter tract with a characteristic C-shape: corpus callosum. Below again, there’s a triangle-like shape: that’s the medial wall of the lateral ventricles. Even below we can see, in the sagittal medial section (pictures on the right), part of the diencephalon: the ovoidal mass is the thalamus and below-front of it there’s the hypothalamus. Ventral view or orbital view If we observe the surface from the bottom (ventral view, or orbital view), we can observe, for the most, cerebral cortex. This part of the brain lays on the cranial fossae. In the medial part, from caudal to cranial, we observe: the brain stem (medulla oblungata, pons, midbrain); a tiny portion of the diencephalon in the central part there’s (the round shaped mammillary bodies, in the posterior hypothalamus); tuber cinereum (also part of the hypothalamus); optic chiasma (where the axons of the nerves arose from the middle part of the retina cross the midline); the elongated bulges in the fronto-ventral brain are the 2 olfactory bulbs and corresponding olfactory tracts. Its olfactory cortex is more caudal. The cortex is gyrified: full of foldings, called gyri, that limit portions of the cortex. This is characteristic of many mammals, but not every: some animals’ brain is smooth (lissencephaly = smooth brain, like rodents and koalas; opposite to gyrencephalic). Gyri expand the superficial area maintaining a small volume. Some severe neuronal disease can lead to lissencephaly. In the brain there are 4 fissures deeper than the others and have a consistent location among individuals (always has the same position in all people): Central sulcus or Rolando’s sulcus: divides the frontal lobe from the parietal lobe. Lateral fissure or Sylvian fissure: divides the temporal lobe from the frontal and parietal lobes. Parieto-occipital sulcus: in the posterior part divides the occipital lobe from the parietal lobe. Calcarine fissure: in the occipital lobe, less deep that the others, but important because it’s a reference point to locate the primary visual cortex (it’s located exactly above and beyond the calcarine sulcus). The position of the sulcus can be, at certain extent, variable among individuals (not the position of the primary visual cortex in relation to the sulcus!). Note: there’s not an actual border dividing the temporal lobe from the occipital lobe! In front and behind the central sulcus there are 2 parallel cortical gyri: gyrus pre-centralis (site of the primary motor cortex, generates voluntary motor control plan) and gyrus post-centralis (site of the primary somatosensory cortex, that receives touch, heat, nociceptive info). These 4 main fissures divide the brain surface in 4 lobes: frontal, parietal, temporal and occipital. We can identify a 5th lobe, not visible from the outer surface of the brain, but observable if we open the 2 margins of the lateral fissures (medial section): the limbic lobe, or insular lobe; divided from the other lobes by a deep sulcus called cingulate fissure. 2.1.4 Inner brain Coronal view We have grey matter in the surface (cortex), and extended white matter below the cortex. This wide extension of white matter, typically human, is called semi-oval centre (sub-cortical white matter) and it’s indicative of the fact that in the brain not only is important to increase the surface of the cortex but much more to increase number and efficiency of connections among different areas (particularly different parts of the cortex). Within the telencephalic white matter are white matter tracts that connect the 2 hemispheres: corpus callosum. Other tracts include axons that, from the cortex, reach other areas of the CNS like brain stem and spinal cord. These descending/ascending axons travel along other white matter tracts: internal capsule, external capsule and extreme capsule. In the internal and medial part are the 2 lateral ventricles (butterfly-shaped cavities containing CSF – cerebrospinal fluid) and the basal ganglia (2 ovoidal grey matter nuclei). Inner brain structures: Diencephalon o Thalamus (just above the midbrain, symmetrical, bi ovoidal grey matter formation) o Hypothalamus (anterior and below the thalamus, connected to a small bulge called hypophysis (endocrine gland in the centre of the brain), linked through the pituitary-hypothalamic tract) o Subthalamus o Epithalamus Basal ganglia: ovoidal grey matter formations deep in the telencephalon, laterally to the diencephalon, composed of an ovoidal mass connected to the nucleus caudatus (comma-shaped nucleus). Brain stem: medulla oblungata, pons, midbrain. 2.2 Diencephalon Functionally and anatomically heterogeneous. The diencephalic structures are located in the medial part of the brain. 1. THALAMUS. It receives all sensory information (except for olfactory), integrates and sends it to the cortex. It’s also involved in motor control because in the thalamus there are specific nuclei connected to the cerebellum and basal ganglia for initiation/motivation to move and adjustments of ongoing movements. 2. HYPOTHALAMUS: (in the picture it’s actually number 3) it’s the main centre involved in body homeostasis. This function is exerted in 2 ways: a. Controls HYPOPHYSIS activity (hormones involved in the regulation of most of our systems) b. Nervous way; it’s the main controller of the autonomic system: there are nuclei involved in the control of the body temperature, blood pressure, caloric income, etc. 3. SUBTHALAMUS: lays below the thalamus, laterally to the hypothalamus; it’s a small grey matter part involved in motor control (connected to the basal ganglia). 4. EPITHALAMUS: in the posterior part of the diencephalon, it’s a small bulge composed of a nervous part and an endocrine part. a. The nervous part is involved in autonomic reflexes triggered by sensory stimuli (like vomit due to disgusting smells, salivation reflex due to good smells, etc) b. EPIPHISIS (also called pineal gland): it’s an endocrine gland important for the production of melatonin (high during the hours of dark and suppressed by light; induces sleep). In some individuals (30%), the 2 thalami are connected by a portion of grey matter called interthalamic adhesion. They don’t exchange info (the connection is not white matter) and it doesn’t seem to affect in any way the thalami functionality. Note the anatomical relations with the ventricles: the thalami form part of the floor of the 2 lateral ventricles; the 3 rd ventricle is in the middle of the hypothalamus. At the sides of the diencephalon, we find the basal ganglia. 2.3 Basal ganglia Grey matter nuclei. From embryological point of view, they include: Corpus striatum: includes lentiform nucleus and nucleus caudatus (comma shaped, above the lentiform nucleus and the thalamus) Amygdala: in front of the tail of nucleus caudatus (it’s included in basal ganglia only from the embryo pov because they originate from the same part of the neuroepithelium; functionally they’re totally different). Amygdala: limbic system; close connection with the limbic lobe and involved in emotional interpretation of stimuli and memories. High activity (fires action potentials at high frequency) when a memory or a stimulus is related to fear. Some diseases lead to fearless behavioural phenotype (like a disease where amygdala’s neurons were calcified). Not good for survival. Basal ganglia: involved in motor control. A little focus on corpus striatum: it’s made of nucleus caudatus (comma shaped) and lentiform nucleus (because of its shape, like a convex lens). The lentiform nucleus is composed by 2 nuclei: Putamen Globus pallidus Between the lentiform nucleus and the nucleus caudatus there are bridges of grey matter that give the nucleus the striatal appearance. Claustrum: an elongated stream of neurons, part of the basal ganglia, its function it’s not quite known, maybe it’s related to the processing of visual info. 2.4 Brain stem The medulla oblungata is related to basic functions and contains centres for the regulation of visceral functions (like the respiratory centre and the cardiac centre). The pons transmits info to the thalamus and cerebellum and includes somatic motor sensors. The midbrain is involved in the processing of visual and auditory info to generate somatic motor reflexes and maintains a state of consciousness. Any problem here (any stroke in the brain stem) leads to fatal or highly severe clinical phenotypes (loss of functions). Locked-in syndrome: the person is locked in their own body, incapable to control it or receive sensory information from the outside. 2.4.1 Medulla oblungata Since there’s no real edge between the medulla oblungata and spinal cord, on the surface of the medulla we can find the same features of the spinal cord. Anterior view Medially in the medulla we have the continuation of the anterior medial sulcus of the spinal cord. Laterally to the medial sulcus, there are round shaped formations called pyramids. They’re white matter tracts that include the pyramidal or cortico-spinal fibers: axons of neurons, whose bodies are located in the primary motor cortex, that convey the motor plan to the spinal cord. The pyramidal pathway is the pathway of the voluntary motor control. In the lower part of the medulla there’s a portion in which the anterior medial sulcus seems to disappear for a moment. This discontinuity is the pyramidal decussation: means that it’s the place where the 85% of the pyramidal axons cross the midline and pass to the contralateral side of medulla 🡪 spinal cord. That’s why the left cortex controls the right side of the body and viceversa. Laterally to the pyramids there are 2 anterior lateral sulci (just like in the spinal cord), from where emerge the 12th pair of cranial nerves (one nerve from the right, one nerve from the left). XII (hypoglossal): controls muscles of the tongue. Laterally to the lateral sulci there are bulges called bulbar olives. Here lay the so called olivary nuclei, closely connected to the cerebellum and the motor pathway (involved in motor control). Laterally to the bulbar olives we observe the emergence of other 3 pairs of cranial nerves: IX (glossopharyngeal) X (vagus): descends along the neck, enters the abdominal cavity and reaches most of the visceral organs XI (spinal accessory nerve) Posterior view There are many sulci (continuation of spinal fessures). In particular, 2 fascicles of axons called fasciculus gracilis and cuneatus: white matter that convey axons to the tuberculum gracilis and cuneatum. These are the 2nd station that receives somatosensory info about high resolution tactile information and proprioception. 2.4.2 Pons Anterior view There’s the bulbar-pontine sulcus that divides the medulla from the pons. Here emerge other cranial nerves (lateral to medial): VIII (vestibular acoustic nerve): info from the vestibular system about balance (position of the head) and hearing VII (facial nerve): motor control of the mimic muscles VI (abducens nerve): one of the 3 oculomotor nerves, it innerves the extrinsic muscles of the eyes to move them within the orbitae Ventral part of the pons is very extended (basis of the pons). Along the midline we can appreciate a depression (not quite a sulcus) called sulcus of the basilar artery that provides the posterior circulation of the brain (2 vertebral arteries that join at the basis of the pons in a single artery). On the lateral side of the basis emerges the: V cranial nerve (trigeminus) Posterior view A little focus on the IV ventricle: part of the cerebellum composes its roof; the floor is composed by 2 triangles (the upper one is part of the pons, the lower one is part of the posterior face of the medulla) that form the rhomboidal fossae. Ammetto che qui ho mancato di scrivere una cosa, ma nella registrazione è saltato l’audio. Se diceva qualcosa di importante, pls inserire (sorry) 2.4.3 Midbrain Anterior view Second horizontal sulcus ponto-mesencephalic sulcus divides the pons from the midbrain. In this sulcus emerges here 2 crania nerves: III (oculomotor): innervates most of the extrinsic muscles of the eye IV (trochlear): emerges from the side of the sulcus; it’s an oculomotor nerve (like VI), and the only cranial nerve that emerges from the posterior part of the brain stem. Laterally er find the cerebral peduncles, a group of fibres where the pyramidal nerves travel. Between the 2 cerebral peduncle there’s a depression called interpeduncular fossae. The surface of the midbrain is full of small holes, entrance points of the vessels, giving this part of the midbrain a perforated appearance called substantia perforata. Posterior view (the cerebellum is removed otherwise the parts below are not visible) In the midbrain there are 4 round shaped formations called colliculi: 2 superior (receive visual info) and 2 inferior (receive auditory info) that overall form the lamina quadrigemina, involved in the generation of motor reflexes that automatically tilt our head and eyes toward the direction of the stimuli. 2.5 Cerebellum Superior view Anterior view The cerebellum is the most dorsal part of the brain, located behind the brain stem. It’s possible to divide it in 2 macro areas. A along the midline, an elevated part is called vermis of the cerebellum (the closest part to the vermis is called paravermial region); laterally there are 2 big cerebellar hemispheres. They are 3 functionally different regions that control movements of different parts of the body and are connected to different parts of the CNS. On the surface there are foldings, overall parallel, that form transverse lamellae on the cortical cerebellar surface. Among these fissures there’s a big one called primary sulcus that divides the cerebellum into an anterior lobe (in the image it’s pink) and a big posterior lobe (in the image it’s green) that forms the most part of the cerebellar parenchyma. The posterior lobe covers most of the extension of the third lobe called flocculo-nodular lobe (most phylogenetically ancient part of the cerebellum, related to the control of balance and eyes movements – oculomotor reflexes to maintain a stable image over the retina). The grey matter is located on the surface, while the inside is white matter (called arbor vitae because it resembles a tree). There are other parts of grey matter in the inner and lateral regions of the cerebellum called deep cerebellar nuclei. Cerebellum and brain stem are connected by the 3 cerebellar peduncles: superior (connects the cerebellum with the midbrain) medial (connects the cerebellum with the pons) inferior (connects the cerebellum with the medulla) 3. ORGANIZATIONAL PRINCIPLES OF THE CNS There are some rules that can apply to the organization of the CNS. The first one is that, when we will deal with grey matter structures, we will see that in these structures the neurons are organized in two ways: Layering. In fact, we will encounter structures such as the cerebral cortex or the cerebellar cortex which are organized in layers. Typically, the human cortex is a 6 layered structure while the cerebellar cortex is a 3 layered structure, but we will also encounter other cortical regions which are made up of lower number of layers. They are grey matter structures in which neurons are organized, so the cytoarchitectonics of the structure allow us to distinguish different layers based on the number and on the type of neurons that are located in different layers. While, in other areas, for example in the basal ganglia, in the Thalamus, or in the Hypothalamus, we will see that neurons are instead organized in nuclei, so in groups of cells somata, neuronal somata, which do not identify a specific layering. So, these are two general organizational types of grey matter neurons. We already know that neuronal axons can group in to fascicles or tracts, when these axons are myelinated they constitute the white matter, and so each grey matter station receives afferent fibres and projects efferent fibres. Afferent fibres are those axons that convey the information to a particular location. Efferent axons, or efferent fibres, are the axons of those neurons embedded in the nucleus that project the information outside of this site. Related to this, we will see that the different cerebral areas are organized in nervous pathways. So they do not function as unique single elements, but they exert their function by collaborating with other structures through which they are connected through afferent and efferent fibres. 4. NERVOUS PATHWAYS In a nervous pathway, different sites are synaptically connected and this kind of collaboration is instrumental to the fact that different parts of the brain process different aspects of information and then, normally, there is a hub region that puts together the different processes. But in a nervous pathway, we can always recognize a sort of hierarchy, a region from which the information starts and then is transferred to the rest of the pathway, and that depends on the type of information it is conveyed. Here is a prototypical example of a pathway, and particularly here on the left you can see a drawing that is a schematic representation of one of the ascending pathways that convey sensory information from the skin up to the primary somatosensory cortex. This is a typical example of a nervous pathway in which you have a peripheral neuron that initially collects information from the periphery (this is a Corpuscle of Pacini, so one of the receptors that we have in the dermis), and as you can see here, we have a centripetal axon that convey this sensory information to neurons that are located in the brain stem, and particularly in the Tuberculus gracilis, or cuneatus, so this is the second station of this pathway. Then we have a third station on the Thalamus and a final fourth station in the Primary somatosensory cortex. This is an example of a nervous pathway in which the hierarchy starts in the periphery, so basically the first order neurons that collect the information as a first element, is hierarchically prominent compared to the rest of the pathway. In a complementary and opposite way, we can see a drawing of the Cortical- spinal pathway, which is a descending pathway, the Pyramidal pathway, and it is the main pathway that conveys the voluntary motor control commands to the periphery. The motor plan is designed in the primary-motor cortex, from neurons that are also called ‘primary’ or ‘superior’ motor neurons, then these neurons project very long axons to reach secondary or inferior motor neurons in the spinal cord, so this is the second station, and finally spinal motor neurons project to the skeletal muscle fibers in the periphery. This is again an example of a nervous pathway but here the hierarchy put the primary motor cortex in a first position, in a hierarchical prominent position. 4.1 Topographic maps Then, another super important rule is the presence of a topographical representation, sort of maps, that we can identify in many regions. These are maps of the periphery that we can design over the surface of different cerebral and spinal regions, and represents the periphery. Basically, the position of neurons that process information coming from specific regions in the periphery, are not organized by chance, but we can identify a map in which, for example, the neurons that process the sensory information coming from the hands, are located in a specific region, while those neurons that process sensory information coming from the head, are located in another region of the same cortical area and so on. In different cerebral and spinal regions we can identify a map of the periphery and two of the most famous maps, that are also called ‘Somatotopic maps’ that we can find in the CNS, are the so called ‘Homunculi’. The Homunculi are maps that have been designed over the surface of the Primary motor cortex (in this case this is the ‘Homunculus motorius’) and over the surface of the Primary somatosensitive cortex (in this case we call this map ‘Homunculus sensitivus’). These are maps that we can design over the surface of these two types of cortexes that represent the position and the abundance of neurons that, in the case of the Homunculus sensitivus, receive the sensory information from a certain peripheral region, or, in case of the motor cortex, process the motor control plan related to a specific district of the periphery. We name these maps as ‘Homunculi’, and not like just ‘Homo’, because they are distorted maps, so these are not really faithful maps of the periphery, but as you can see here, different parts of the body are represented in a distorted way. For example, as regards the primary motor cortex we can identify regions that are particularly extended in the brain compared to the periphery such as the hands, the fingers, the face, which is related to the motor control of the mimic muscle, the tongue and also the larynx (the structure that allow us to articulate language). So, these peripheral regions are particularly extended in these maps because the number of neurons that process the motor control of these regions is high. That means that we spend a lot of neurons to control the movement of the areas, which are particularly important to our human functions. That relates to the function of our hands, the possibility to have a mimic communication with our co-specifics, and particularly with the language. The same applies to the somatosensory maps, that we will see when we’ll study the cerebral cortex. In the primary somatosensitive cortex we can design a Homunculus sensitivus in which again we have different parts that are represented as large regions in the map, and again face, mouth and hands occupy large portions of this map, while whole regions such as the back, or the skin of the trunk are represented as smaller areas because we have a lower number of receptors in the skin, and a lower number neurons in the somatosensory cortex which process sensory information from these parts. These maps were designed by a physiologist, Penfield (he lived in the first 30 years of the 20th century). He was an electrophysiologist and in an awake patient he applied electrical stimuli over the surface of the cortex and asked the patient to express the position in which he or she felt a sensory stimulus based just on the electrical stimulation on the surface of the cortex, or by just observing the contraction of the different parts of the body induced by the electrical stimulation of particularly subsections of the primary motor cortex, and so he designed this sort of maps. In the cortex we have these very well designs of the periphery, but we will see that similar maps, perhaps less accurate, can be identified also in the spinal cord or in some nuclei of the Thalamus or Cerebellum, so in most cerebral and spinal regions we have somatotopic maps of the periphery. That means different parts of those grey matter neurons are devoted to the control of different part of the periphery. There is a final general rule that applies to most systema, except one: functional systems control the activities of the contro-lateral side of the periphery. It is a known concept that, for example, the left motor cortex controls the movements of the right part of the body, and vice versa, and this applies also for the sensory cortex so the left somatosensory cortex receives the tactile stimulation coming from the contro-lateral part of the body. It means that the nervous pathway crosses the midline and passes to the contro-lateral side at a certain level of the pathway. This rule applies to most systems with the exception of the Cerebellum, which has an ipsi-lateral control of the body, and this is due to the fact that the nervous pathways that involve the Cerebellum, in one case do not cross the midline, or in another case they cross the midline twice. That means that when we have a lesion on the right hemisphere of the Cerebellum, the control that we lose is over the right part of the periphery, and the same for the other side. 5. MICROSCOPIC ANATOMY OF THE NERVOUS SYSTEM Nervous Tissue: The Nervous Tissue is the tissue specialized in conducting electrical impulses. When we talk about neuronal impulses, we talk about action potentials that are conveyed along axons. The nervous tissue is composed by two cells types, two main categories: Neurons Glial cells In this slide we see a very prototypical example of neurons surrounded by glial cells, however this is a very particular example, because this is a microscopic image from a slide of a dorsal root ganglion in which we can see neurons (the big somata that are recognizable as neurons because we can appreciate this very evident nucleolus), which are surrounded by these small spots, which are the Satellite Glial cells. Our concept of the cytoarchitecture of the nervous system comes from the debate that was active between Santiago Ramon y Cajal and Camillo Golgi in the first years of the 19th. Camillo Golgi was a neuropathologist, sited in Pavia. Santiago Ramon y Cajal is the father of Neuroanatomy and was a Spanish neurologist. Both received the Nobel price for their studies but they were on opposite positions. Golgi thought that neurons were indeed not single cellular elements, but a network, a syncytium in which the cells were not divided one by the other, by they were just a continuous network which extended for all the CNS. Santiago Ramon y Cajal proposed the Neuron Theory, or Cellular Theory, in which he proposed that neurons were indeed singular element that were connected somehow with the others, but not in continuity with other elements, Now we know that Santiago Ramon y Cajal was right and Golgi was wrong. At that time, they had experimental evidence for both theories, because science at that time was not able to distinguish between the two possibilities. Santiago Ramon y Cajal is also an important person for neuroanatomy, we also use his drawings because he was interested in both medicine and figurative arts, and built up a special instrument, the Camera lucida (an optical microscope connected with a chain of mirrors that projects the image of the lens over a surface, such as a paper sheet), and in this way he was able to design the morphology of most cell types we have in our brain. So even before knowing of the neurons and functions of the different types of glial cells, he was able to design them in a very detailed manner, and also to hypothesized function and organization of the cells just based on their appearance and on his drawings that are really faithful to reality. They are models by which we explain morphology of the neurons that now we look at with super microscopes. 5.1 Neurons Neurons are cells specialized for reception of different stimuli. The transduction of different stimuli consists in the transformation of the stimulus in impulses, in trains of action potentials. They’re also specialized in the processing of stimuli and their conduction, and also in their transmission to other cells. From a functional point of view, neurons can be divided in: Sensory neurons, specialized in receiving different types of sensory stimuli Motor neurons, or effector neurons, so those neurons that project information to the periphery, so they don’t receive anything, they project a command to the periphery And in the middle, Interneurons or Association neurons, which connect the two compartments Neurons are characterized by a big cell soma from which a certain number, multiple, dendrites extend. Dendrites are those neuronal processes that operate as an afferent compartment, so they receive the stimulus from other neurons and then from the cell somata we have the extension of just one axon. Axons can branch during their course, but when they exit from the cell somata, neurons have just one axon. Axons operate as an efferent compartment of the neuron, so the cellular compartment that convey information outside, and to a post synaptic neuron. At the end of the axons we fin synaptic buttons, which are enlargements of the axons, in which we can find the repertoire of molecules and vesicles of neurotransmitters which consist in the so called ‘pre-synaptic compartment’ of the synapsis. Another element that we can see is the presence of myelinated portions that are indeed myelin tracts which are called ‘Internodes’. They are those axons tract that are covered by myelin, which is not a continuous ensheathment of the axon, but it’s an interrupted ensheathment, consisting in multiple internodes which are interrupted by naked portion of axons, which are called ‘nodes’, particularly ‘Nodes of Ranvier’. They are those naked portions of axons in which voltage dependent sodium and potassium channel are clustered together allowing the regeneration of the axon potential; so this myelination arrangement allows the so called ‘saltatory conduction of the axons potential’, which is the evolutionary strategy that was followed by vertebrates to increase the velocity of the action potential conduction without increasing the axon’s diameter. Since neuronally impulses are basically electrical stimuli, two strategies would be in principle followed: Insulation of the cable, the myelination. Which is the strategy that allowed the vertebrates to increase a lot the rate of action potential conduction while maintaining the diameter to the axons relatively small The alternative strategy that was instead followed by some invertebrates, was increasing the diameter of the axons and that’s why the first experiment related to the action potential were made in invertebrates, particularly in the squid, in which we can find the prototypical squid axons, that are unmyelinated and super big, which convey action potential at relatively high speed just because they are very big so they allow the transfer of big number of ions, of currents, along the axons. Regarding the morphology, the neurons can be divided in 3 categories: Multipolar neurons Bipolar neurons Pseudounipolar neurons 5.1.1 Multipolar neurons Multipolar neurons are 95% of the neurons we have in the nervous system. They’re typical neurons with a lot of dendrites and just one axon. As you can see in these images, when we say ‘multipolar neurons’ we are referring to a different and morphologically heterogeneous type of neurons, that are pretty much different to the prototype always represented in textbooks. In the first two images you can find microscopic images of pyramidal neurons of the cerebral cortex. This is an immunohistochemical layer of neurons. In layer 5 we have this cells that are called in fact ‘pyramidal neurons’, the most abundant neuronal cell type we have in the cortex, 80% of the cerebral cortex neurons are indeed pyramidal neurons. Here we can see just 3 of them, but you have to imagine a plethora of these neurons. They are called pyramidal because they have a triangular shaped cell somata from which a low number of horizontal dendrites extend in the same layer in which the cell somata is positioned. And, as you can see these cells extend one very long apical dendrite that goes up and reaches the first layer of the cortex, the most superficial layer, in which it branches in a sort shaft. We cannot see in this image but can be appreciated on the image on the left, on the other pole these neurons extend one axon that projects downward. It is a myelinated axon that will enter the semi-oval centre, which will be embedded in subcortical white matter. In the Cerebellum other multipolar neurons are different from those we saw. In this image we can see the ‘Granule cells’ or ‘Granule neurons’ of the Cerebellum. They are called ‘Granule’ because they are super small. These are the most abundant neurons in our brain and have a small round shaped cell somata from which 4 to 6 very short dendrites extend. And then, they have one axon that instead goes up and reaches the most superficial layer of the cerebellar cortex dividing in two branches which become the so called ‘parallel fibers’, because they travel parallelly to the surface of the cortex. In the Cerebellum we have another type of multipolar neurons, which is the Purkinje cell neuron. These are super big neurons with a big cell soma, around tenfold times bigger compared to the granules, more or less 15 µm in diameter, from which a proximal big dendrite extend; from this we can appreciate the extension of the ramifications of the dendritical tree, which extend in the most superficial layer of the cerebellar cortex (called molecular layer). On the opposite side, a single axon descends from the cell soma in the deeper part of the cerebellar cortex. This is again a myelinated axon that will enter the cerebellar white matter. These are prototypes of multipolar neurons to appreciate the variety of morphologies of neurons adapting to the different circuits they are involved in. 5.1.2 Bipolar neurons This category is much less diffused: the bipolar neurons. We have a cell soma from which we have one axon on one side and one dendrite on the other side, so cells are bipolar in shape. These cells are located, for example, in the retina (one retinal layer includes neurons that are called in fact ‘bipolar neurons’) but we also have them in the olfactory mucosa (neurons that first collect smell information) and in the acoustic and vestibular ganglia (which are the ganglia that collect information from the vestibular system and inner ear, so the cochlea). In this image we can see a microscopy of the acoustic ganglia, where in some cases, when the angle of the cut of this slice is perfectly parallel to the extension of the dendrite and the axon, we can appreciate the extension of these two processes from each of these cells somata. 5.1.3 Pseudounipolar neurons The third category are Pseudounipolar neurons, which are again very poorly diffused. They are typical of the ganglia, particularly of the dorsal root ganglia of the spinal nerve. These are called ‘Pseudounipolar’ because they have one big circular soma from which just one process extends but then when this process exits from the ganglion it divides in two processes: One is directed toward the periphery and it is called ‘centrifugal process’ or ‘peripheric process’, and it is a fiber that will reach a mechano-receptor o dermal receptor in the dermis, or proprioceptors embedded in the muscles, so peripheral sites. The second process instead is the ‘centripetal process’ or ‘central process’ which will enter the spinal cord. These neurons are called Pseudounipolar because they are bipolar neurons but the morphology makes us think they are unipolar. 5.2 The synapse Synapses are the site in which the electrical impulse is transformed in a chemical form of communication. When axon potential travels along the axon, it reaches the final portion of the axon, the synaptic button, in which the depolarization of the membrane induces the opening of calcium channels; increasing of the intracellular calcium induces exocytosis of vesicles that are clusters located in the pre-synaptic buttons, and the exocytosis of the vesicles allows the release of a certain neurotransmitter in the so called ‘synaptic cleft’. On the post-synaptic site, we will have a portion of the cell membrane where molecular receptors (specific for that neurotransmitter) will bind with their ligand and will change their conformation. Depending on their type (if they are metabotropic receptors or ionotropic receptors) this change in conformation can activate a signaling pathway within the post-synaptic neurons (in case of the metabotropic receptors), or they will open or close an ion channel and so changing the balance of ions such as sodium, potassium, calcium or chloride (in the case of ionotropic receptors), and this can eventually lead to a depolarization of that portion of the membrane of the post-synaptic neuron, or a hyperpolarization of that portion. Depolarization means that the voltage goes up, which means the voltage of that part of the membrane becomes closer to the threshold that allows the generation of the action potential. Hyperpolarization means the voltage goes down, so it becomes more distant compared to the threshold. This is a typical arrangement of neuron-to-neuron synapses, but we know that we have also neuro-something junctions in which neurons can release neurotransmitters in a post-synaptic element which is not a neuron. Therefore, we can have neuro-muscular junction, when the post-synaptic elements a skeletal, a smooth or a cardiac muscle element; or neuro-glandular elements when the post -synaptic elements a endocrine or exocrine cell, so when the neurotransmitter release regulates the activity of a gland cell. 5.2.1 Neurotransmitters Neurotransmitters are molecules that are collected within synaptic vesicles which are clustered in the synaptic buttons. In the CNS the most diffused excitatory neurotransmitter is Glutammate, that is extremely diffused in all sites of CNS. In a complementary and opposite way, the most diffused inhibitory neurotransmitter is GABA, Gamma-ammino- buthirric-acid. We have a plethora of other molecules that have a more restricted distribution in the CNS and in most cases do not operate as principal neurotransmitters but as neuromodulators. They do not have a primary role in neurotransmission but regulate in a positive or negative way, so potentiate or repress the neurotransmission mediated by other types of neurotransmitters, basically Glutammate or GABA. Acetylcholine is a primary neurotransmitter in the autonomic system, while in the CNS it is restricted only to some regions and particularly. We have a colinergic neurotransmitter in the cerebral cortex, so release of acetylcholine in the cerebral cortex, in the Thalamus and Cerebellum, but here it operates as neuromodulator, not as a primary neurotransmitter. It is normally co-released with Glutammate or GABA. Other molecules that are also important from the clinical and pharmacological point of view are: Norepinephrine, which is Noradrenaline, that again operates as a primary neurotransmitter in the autonomic system, particularly in the Sympathetic system, while in the CNS it is just released by a restricted type of neurons located in the Locus Ceruleus of the Pons and in this lateral tegmental area (Locus Ceruleus is a prototypical noradrenergic nucleus), and these neurons project diffusely to the CNS where Noradrenalin exert a neuromodulatory effect, (for example in the cerebral cortex). Dopamine is used by neurons of the Midbrain, particularly by two types: those in the Substantia nigra and those located in this ventral tegmental area. These neurons project to basal ganglia. Dopaminergic neurons of the Substantia nigra are those neurons that degenerate in Parkinson Disease and it is the loss of dopaminergic transmission the cause of the emergence of clinical symptoms associated with PD. That’s why a typical drug that is used for patients with Parkinson Disease is ‘Levodopa’, a dopamine-mimetic form that can overcome the BBB (Brain Blood Barrier) and that can enter the brain. On the other side, the VTA, this ventral tegmental area, projects in to the Nucleus Accumbens, and it’s part of the so called ‘reward system’, the circuit that mediates our feelings of pleasure, and this is the system on which a plethora of drugs of abuse operate by increasing the release of Dopamine from VTA to Nucleus Accumbens. Serotonin is another important neuromodulator from a clinical and pharmacological point of view. Serotonin is just released by a subset of neurons that are located in the Brain Stem: the RAFE neurons. These neurons project diffusely to the other CNS regions, particularly to the cortex and prefrontal cortex, and Serotonin is notable because the serotoninergic transmission is one of those most repressed in major depression, and a typical anti-depressant drug, ‘Fluexitin’, is indeed a modulator of the serotoninergic transmission, and particularly is an inhibitor of Serotonin reuptake from the synaptic cleft, so they increase the availability of Serotonin at the synapses. Histamine is used by two particular population of neurons in the Hypothalamus and the Reticular formation, and project diffusely to the cerebral cortex and release of Histamine activate the cortex, so it is involved in increasing alertness, and that’s why when we take anti-histaminergic drugs for allergy, one typical side effect is sleep, and this is due to the fact that we are suppressing the histaminergic transmission over the cortex so we are saying to the cortex that is the moment to sleep. Glycine is expressed mostly in the spinal cord and together with GABA it operates as an inhibitory neurotransmitter. This is a list of common drugs that exploit the neurotransmission to have an effect on different aspects of behavior or autonomic effects mediated by the nervous system. 5.2.2 Dendritic spines Dendritic spines are small protrusions that are typical of the dendrites of projections neurons in different parts of the brain, for example here we have a drawing of a pyramidal cel

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